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An exceedingly exclusive club recently welcomed two new members, with the publication of the complete genome sequences of an African and a Chinese man in the November 6 issue of Nature. That brings to four the number of people who have had their personal genetic code read in its entirety. James Watson, co-discoverer of the double helix, and sequencing pioneer Craig Venter were the first two. Now, they are joined by a pair of anonymous individuals, as a group led by David Bentley of Illumina Cambridge Ltd. in Essex, UK, reports the complete genome of a Nigerian man, while Jun Wang, Jian Wang and colleagues from Shenzhen University, China, release the genetic makeup of a Han Chinese man. No women in the club as of yet.

The new genomes were accomplished in a fraction of the time and cost of the Watson and Venter efforts, and the accomplishment moves researchers one step closer to the goal of routine personal genome sequencing for medical and research purposes.

Both groups used massively parallel chip-based sequencing techniques that can produce 100 million short 35 base-pair sequences at one time. Using multiple chips, the groups generated between 4 and 17 billion bases worth of sequence data per week (the complete human genome has about three billion bases). The short reads were assembled using the existing reference genome as a template. In eight weeks, at a cost of $250,000 for reagents, the Bentley team produced 135 billion bases of sequence, an average 40-fold coverage of the genome. The Wang team had comparable output at a price they put at less than $500,000. For comparison, Watson’s genome cost $10 million to complete, at 7.5-fold coverage.

Because of the high coverage rate, the sequences were highly accurate. For example, 99 percent of the roughly 3 million known single nucleotide polymorphisms (SNPs) were confirmed, and an additional million more SNPs were identified. The incidence of insertions and deletions was similar to that seen with the previous work, although the technique preferentially detected deletions and small insertions.

“The approach of Bentley, Wang and their colleagues represents a substantial advance in the sequencing of individual genomes,” write Samuel Levy and Robert Strausberg of the J. Craig Venter Institute of Rockville, Maryland, in an accompanying commentary. “They reinforce the catalog of variants that exist in human genomes—SNPs in the millions, insertion/deletion polymorphisms in the hundreds of thousands and structural variants in the thousands.”

Interestingly, the Chinese man appears to have an elevated risk for Alzheimer disease based on his APOE and SORL1 alleles, but there is no family information available that might indicate a history of AD. Assigning risk using known genes is one important application of personal genomics. Another is using genotype-phenotype associations to uncover genes and variants associated with disease, an effort that will depend on having many more individual genomes. With both the Chinese and British groups participating in the 1000 Genomes Project, the "completely sequenced" club might be looking at a major boost in membership soon.—Pat McCaffrey